WHO, Health Canada, TGA, FDA EU and Cleaning Validation.
Regulatory Requirements.
Information & Training. | Product & Process Validation.
European (EU) and International Conference on Harmonisation (ICH) Q7A expectations detail that sample testing should include swabbing, rinsing or alternative methods (e.g., direct extraction), as appropriate, to detect both insoluble and soluble residues. The Cleaning Validation sampling methods used should be capable of quantitatively measuring levels of residues remaining on the equipment surfaces after cleaning.
The US Food and Drug Administration’s “Guide to Inspections Validation of Cleaning Process” states that there are two general types of sample testing that have been found acceptable. The most desirable is the direct method of sampling the surface of the equipment. Another method is the use of rinse solutions.
Health Canada, Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S), and World Health Organization (WHO) guidelines detail an expectation that in general that there are two methods of sampling that are considered to be acceptable: direct surface sampling (swab method) and indirect sampling (use of rinse solutions). A combination of the two methods is generally the most desirable, particularly in circumstances where accessibility of equipment parts can mitigate against direct surface sampling.
All cleaning validation sampling methods will normally include a visual check which will provide an immediate feedback on the cleaning process deficiencies. The sampling method will then be based on some or all of surface swabbing, sample fluid rinse, coupon sampling, placebo sampling.
Swabbing involves using a wipe or swab that is moistened with high purity water (WFI – water for injection) that is typically wiped over a defined area in a systematic multi-pass way always going from clean to dirty areas to avoid recontamination – i.e. 10 side by side strokes vertically, 10 horizontally and 10 each with the flip side of the swab in each diagonal direction. For TOC analysis very clean low background swabs or wipes and sample vials such should be used.
Rinse water sampling involves taking a sample of an equilibrated post-final rinse that has been re-circulated over all surfaces. Rinse samples should be correlated to a direct measuring technique such as swabbing.
Coupon sampling involves the use of a coupons or an actual removable piece of pipe that is dipped into high purity water to extract residues for analysis.
Placebo testing involves using placebo product and analyzing for residues from the previous batch.
Information & Training.
Product and Process Validation.
- The Validation Master Plan. Performing a Gap Analysis. Validation in the Design Process. Etc..
- How to ensure Validation efforts are aligned with potential Risks.
- How to ensure that Validation activity is appropriately documented, reviewed and aligned with requirements.
- Information & Training presentation >>>
US Food and Drug Administration’s “Guide to Inspections Validation of Cleaning Process”
European (EU) and International Conference on Harmonisation (ICH) Q7A